Failure of sputum eosinophilia after eotaxin inhalation in asthma.

BACKGROUND: Eotaxin is a chemokine specific for eosinophils and may play an important role in eosinophil recruitment in asthma. The effects of eotaxin inhalation on sputum and blood eosinophils, exhaled nitric oxide (NO), and bronchial responsiveness were determined. METHODS: Eotaxin was administered by nebulisation to asthma patients in three studies: (1) an open dose finding study with eotaxin (5, 10 and 20 microg) to two asthmatic subjects; (2) a randomised placebo controlled study with 20 microg eotaxin to five asthmatic subjects and five normal volunteers; and (3) a randomised placebo controlled study with 40 microg eotaxin to nine asthmatics. Forced expiratory volume in 1 second (FEV(1)), exhaled NO, and blood eosinophils were measured before and hourly for 5 hours after nebulisation and at 24 and 72 hours. Methacholine bronchial challenge and sputum induction were performed before and at 5, 24, and 72 hours after nebulisation. RESULTS: In the two placebo controlled studies there was no change in sputum eosinophil count and sputum eosinophilic cationic protein concentration after eotaxin inhalation compared with placebo. FEV(1), exhaled NO, and methacholine PC(20) did not change. However, high dose eotaxin (40 microg) induced an increase in sputum neutrophil count compared with placebo (p<0.05). CONCLUSIONS: Inhaled eotaxin up to 40 microg induced no changes in sputum eosinophil count but at 40 microg it increased the sputum neutrophil count. The significance of this finding is unknown.

Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma.

BACKGROUND: Interleukin 5 (IL-5) has an important role in mobilisation of eosinophils from the bone marrow and in their subsequent terminal differentiation. A study was undertaken to determine whether inhaled and intravenous IL-5 could induce pulmonary eosinophilia and bronchial hyperresponsiveness (BHR) independently of these effects. METHODS: Nine mild asthmatics received inhaled (15 microg) or intravenous (2 microg) IL-5 or placebo in random order in a double blind, crossover study. Blood samples were taken before and at 0.5, 1, 2, 3, 4, 5, 24, and 72 hours following IL-5 or placebo, and bronchial responsiveness (PC(20) methacholine) and eosinophil counts in induced sputum were determined. RESULTS: Serum IL-5 levels were markedly increased 30 minutes after intravenous IL-5 (p=0.002), and sputum IL-5 levels increased 4 and 24 hours after inhaled IL-5 (p<0.05). Serum eotaxin was raised 24 hours after intravenous IL-5 but not after inhaled IL-5 or placebo. Blood eosinophils were markedly reduced 0.5-2 hours after intravenous IL-5 (p<0.05), followed by an increase at 3, 4, 5, and 72 hours (p<0.05). Sputum eosinophils rose significantly in all three groups at 24 hours but there were no differences between the groups. Bronchial responsiveness was not affected by IL-5. CONCLUSION: The effects of IL-5 appear to be mainly in the circulation, inducing peripheral mobilisation of eosinophils to the circulation without any effect on eosinophil mobilisation in the lungs or on bronchial responsiveness.

Eotaxin levels and eosinophils in guinea pig broncho-alveolar lavage fluid are increased at the onset of a viral respiratory infection.

In previous studies we found that guinea pigs demonstrate an increase in airway reactivity and eosinophil numbers 4 days after a respiratory infection with parainfluenza-3 (PI3) virus. Clinical data support the possible involvement of eosinophils in virus-induced airway hyperresponsiveness. Eotaxin, a newly discovered chemokine, could be involved in eosinophil migration to the airways. In this study, eosinophil numbers were counted in blood and bronchoalveolar lavage (BAL) fluid and related with eotaxin concentrations in BAL fluid 1, 2, 3, and 4 days after intratracheal PI3 virus administration. On day 1, blood eosinophils increased by more than 200% (P < 0.01). The number of eosinophils were only slightly enhanced from day 2 to day 4 (40%-70%). BAL fluid eosinophils were not increased on day 1 but were significantly elevated on day 2 (180%) and remained high on days 3-4 (>300%, P < 0. 05). This increase in lung eosinophils correlated well with eotaxin levels measured in BAL fluid. There was no significant increase in eotaxin on day 1 following PI3 infection; however, on days 2-4 eotaxin levels in BAL fluid were significantly elevated (four-sixfold increase) when compared with medium inoculated controls. Eotaxin appears to play an important role in eosinophil accumulation in guinea pig lung following PI3 infection.

Feasibility of enzymatic hydrolysis and alcoholic fermentation of starch contained in buffalo gourd (Cucurbita foetidissima) roots.

The suitability of using annually grown, carrot-sized buffalo gourd (Cucurbita foetidissima) roots as a feedstock for alcoholic fermentation was explored. Roots grown in 1982 and 1983 were slurried, dextrinized and saccharified using Takathermtrade mark and Diazymetrade mark (commercial enzymes manufactured by Miles Laboratories), and fermented by the action of Saccharomyces cerevisiae. These processes were monitored in detail and results were compared with those displayed by controls formulated using potato tubers. The preparation of gourd root slurries with suitable viscosity characteristics for enzymatic digestion required the addition of water (at least 50% by weight) which reduced the proportion of fermentable sugars in the resulting saccharified suspensions. The resulting slurries were well-suited to enzymatic conversion of starch to sugar. Estimates of enzymatic efficiency in gourd root suspensions did not suggest the presence of naturally occurring amylase or glucosidase inhibitors in these plant materials. Saccharified gourd root mashes supported yeast growth well and produced ethanol yields at 82.2-86.5% of the theoretically maximum efficiency.